PROJECT SUMMARY ? Clinical Core The Clinical Core (CC) supports and promotes research that advances the ADC's goal of understanding the complex determinants of cognitive impairment and dementia in diverse older adults. The Core recruits and maintains a large (410 active case) longitudinal cohort (LC) that is ethnoracially and demographically diverse, that has been followed longitudinally for many years, and that is richly characterized with measures that include sophisticated neuropsychological tests and state-of-the-art neuroimaging. This cohort supports multiple R01s and has provided the basis for over 200 papers. The features of the cohort are closely linked to the four scientific themes of the ADC. In accordance with our interest in studying preclinical disease and diagnostic transitions (Theme 1), most cohort participants (60%) were enrolled when cognitively normal and 31% of the overall cohort has transitioned to a more impaired diagnostic status. Cognitive decline, even in the cognitively normal, has been readily measurable. Thus, the LC provides an excellent resource for studies of change and trajectory. Due to community recruitment, the LC is highly diverse (>40% Hispanic or African American, >20% with under 12 yrs. education) and provides excellent heterogeneity in lifecourse factors that may influence cognitive reserve and resiliancy (Theme 2). The cohort has representative prevalences of the common vascular risk factors and most cases have multiple pathologies at autopsy, providing a valuble resource for studying mixed pathology (Theme 3). The CC works closely with the OR Core on recruitment and retention of the LC. The CC consents, evaluates participants annually, and obtains autopsy pre-consents. The CC supports recruitment for funded research projects, including ADC pilot studies. The CC maintains a Clinical Trials Unit that conducts industry and academic sponsored treatment trials. The CC provides reliable and valid diagnoses. It provides a broad set of measures, extending well beyond the UDS, which are collected on a standardized schedule and selected to support the scientific themes. It collaborates with the Neuropathology Core to obtain DNA, serum and plasma samples (supporting Theme 4 on Biomarkers), facilitate brain procurement/autopsy, and to present monthly Clinical Pathological Conferences. The CC coordinates with the Neuroimaging Core to obtain serial structural MRI/resting state fMRI, and molecular imaging PET studies. The CC works closely with the Administrative Core to plan subject recruitment and data collection protocols; with Data/Biostatistics to promptly transfer CC data into the database and maintain quality control; and with REC to educate/mentor AD researchers. RELEVANCE: The CC supports many research projects relevant to advances in the early detection, diagnosis, and treatment of dementia. The CC aims to advance our understanding of how various risk and protective factors affect cognitive trajectories across the spectrum of cognitive aging in our ethnically-diverse cohort. Understanding the factors (biological and lifestyle) which accelerate or protect against cognitive decline could foster healthy brain aging and have a major impact on the public health.